Colorimetric and Fluorometric Determination of Fluoride in Tetrahydrofuran and Dimethyl Sulfoxide Using a 4-Hydroxypyrene Probe

F– ions (fluoride ions) are crucial in various chemical waste and environmental safety contexts. However, excessive fluoride exposure can pose a threat to human well-being. In this study, a simple 4-substituted pyrene derivative known as 4-hydroxypyrene (4-PyOH) was designed as a colorimetric probe for detecting F– through the formation of hydrogen bonds between F– and a hydroxyl group. The probe 4-PyOH exhibited exceptional sensitivity and selectivity towards F– ions and was successfully utilized as test strips for detecting F– ions in organic solvents. The detection limit reached an impressively low level of 3.06 × 10−7 M in the organic solvent. The recognition mechanism was confirmed through 1H NMR titration.


Introduction
Pyrene is recognized as one of the paramount fuorophores owing to its remarkable chemical and photophysical characteristics.Notably, it exhibits substantial Stokes shifts and high quantum yields, which have garnered enduring interest in scientifc circles [1][2][3][4].In addition, pyrene can be readily modifed by specifc chemical modifcations to improve their photophysical properties [5][6][7].Pyrene-based fuorescent probes have widely been used to detect various ions, small molecules, and reactive species [8][9][10][11][12][13].However, research on pyrene has primarily concentrated on the frst position, while investigations regarding the second and fourth positions are relatively limited [14,15].Te properties of pyrene are infuenced not only by various substitution groups but also by the substituents at the generation position.Tis indicates that unorthodox substitution of pyrene holds signifcant research value.
Fluorescence sensors are often the preferred choice for measuring F − compared with the traditional detection techniques attributed to their low cost, simple operation, high sensitivity, and rapid response [16][17][18].Recent literature suggests that the F − probes mainly include the following four mechanisms [19][20][21][22]: hydrogen bonding between F − and hydroxy or amino group in the sensor, the chemical reaction between boron and F − , F − Lewis acid interactions, and F − induced cleavage reactions.Among the mechanisms above, many reported F − probes are based on the hydrogen bonding mechanism, where F − induced deprotonation of hydroxy groups leads to the formation of phenolate anions and distinct color and fuorescence changes.Up to now, there have been many reports of F − detection based on naphthalimide, rhodamine, borondipyrromethene (BOD-IPY), etc.Nevertheless, few researchers pay attention to applying pyrene-based fuorescent probes for F − (see Table S1 in support information).Hence, our research aims to develop a highly sensitive pyrene-based fuorescent probe to detect F − .
Fluorine and fuoride are widely used in various industrial felds [23,24], and fuorine additives are signifcant solutes in the same electrolyte [25].However, when lithium batteries are dismantled, the resulting electrolyte waste can be released into the environment, leading to compounds containing fuorine, arsenic, and phosphorus [26,27].Moreover, organic solvents, such as tetrahydrofuran and dimethylsulfoxide, are of paramount importance as the primary liquid components in lithium batteries, contributing signifcantly to the overall performance and efciency of the batteries [28,29].Te electronic semiconductor industry also utilizes hydrofuoric acid during etching [30][31][32].Similarly, the chemical fertilizer, pesticide, chemical, and petrochemical industries either employ fuorine-containing chemicals or generate fuorine-containing chemical byproducts [33].Consequently, fuorine contamination caused by the industrial related wastes poses a threat to the environment as well as the individual's health and safety of working factory.Given the above thinking, monitoring and easy-to-read detection of fuoride ions have become a necessary and very important research study.
Tis study successfully designed and synthesized a novel fuorescence probe called 4-PyOH based on the pyrene structure.Te probe utilized the phenolic -OH group as a recognition site for the rapid and highly sensitive detection of F⁻.Te design strategy focused on introducing a hydroxyl group at the 4-position of the pyrene molecule, as the electron cloud density at this position was lower than the 1position.Consequently, the hydroxyl group in 4-PyOH exhibits increased acidity, making it more prone to deprotonation and generating its phenolate anion.Te phenolate anion possesses distinct photophysical properties, which enable efective and efcient fuorescence detection of fuoride ions.

Experimental
2.1.Materials and Instrumentation.Te tetrahydrofuran (THF) and dimethylsulfoxide (DMSO) used in the spectral analysis were purchased at the high-performance liquid chromatography (HPLC) level and dried to remove the dissolved water before use.

Synthesis.
Te detailed steps for synthesizing probe 4-PyOH in Scheme 1 have been reported in a previously published paper [14].Briefy, commercial pyrene was hydrogenated to form 1,2,3,6,7,8-hexahydropyrene (compound a), which was then converted into a 4-bromosubstituted pyrene-based compound b in solvent HAc.Subsequently, intermediate b underwent methoxylation catalyzed by CuI, resulting in the formation of compound c.In the following step, compound c was easily transformed into compound d through dehydrogenation oxidation in the presence of DDQ, yielding a high yield of 90%.Finally, the desired 4-PyOH was synthesized by classical demethylation of the methoxyl group with a yield of nearly 100%.

General Procedure for Optical Studies. Probe 4-PyOH
was dissolved individually in dry THF and DMSO to prepare stock solutions with a concentration of 1 mM.Te stock solutions of F⁻ were prepared separately using tetra-nbutylammonium fuoride (TBAF) in dry THF and DMSO at a concentration of 1 mM.Subsequently, the stock solutions were appropriately diluted to a suitable concentration for the experimental procedure.Te fuorescence measurements were conducted at room temperature using an excitation wavelength of 365 nm, with both the excitation and emission slits set at 5 nm.

1 H-NMR Experiments.
Four nuclear magnetic tubes were each loaded with 6 mg of 4-PyOH and 0.6 mL of d 6 -DMSO to facilitate dissolution.TBAF solutions at 0 eq, 1.0 eq, 2.0 eq, and 3.0 eq equivalents were sequentially added to the respective solutions.After 10-minute incubation at room temperature, 1H-NMR spectra were acquired for analysis.

Paper Strips.
To facilitate the portable application of probe 4-PyOH, the test papers were prepared by immersing flter papers with unifed shapes in dichloromethane (DCM) solution of 4-PyOH (2 mM) for 5 minutes and then drying those test papers under a nitrogen atmosphere at room temperature for 10 h.For the detection of F − , the prepared test papers were dipped into dried THF solution with different concentrations of TBAF (0 mmol/L, 1 mmol/L, 5 mmol/L, 10 mmol/L, 50 mmol/L, 100 mmol/L, and 200 mmol/L).Journal of Analytical Methods in Chemistry the emission peak at 382 nm gradually decreased, while the emission peak at 502 nm gradually increased (in the dry THF).At the same time, the fuorescent emission gradually shifted from blue to yellow.Similar phenomena were observed when detecting the F -in dry DMSO; however, its sensitivity was not as fast as in THF and color changes were slower than in THF as well.Tese phenomena indicated that the probe could be applied to detecting F -in organic waste with high sensitivity and readable convenience.To further study the sensor properties of the probe for F -, titration experiments were carried out in dried DMSO and the THF (Figure 1).After three parallel tests, the detection limits were calculated based on the ftting results (Figure S1) and the formula [34]: detection limit � 3σ/k.σ represents the standard deviation of the blank sample, while k denotes the slope of the relationship between the fuorescence intensity ratio and the concentration of F − .According to the formula, the detection limits of the probe were calculated to be 3.06 × 10 −7 M in THF solution and 9.82 × 10 −7 M for F -in DMSO.Moreover, the antiinterference ability of the probe was evaluated by measuring the absorption spectra of fuorine ions in the presence of other competing ions.Te selectivity of 4-PyOH was studied by adding anions (Cl − , Br

Results and Discussion
, NO 3 − , AC − , S 2− , 200 μM, respectively) in dry DMSO (Fig. S2).Tere was no clear absorption diference when competing ions were added to the probe solution.However, upon the addition of 30 μM F − , absorption spectra presented an obvious expansion in 400-500 nm.Te results indicated that 4-PyOH was highly selective to F − with complicated multi-ions' situation.With the change in the absorption spectra, the color of the 4-PyOH solution changes from colorless to yellow in the presence of F − , showing that this "naked-eye" probe can be used for specifcity determination for F − as well.
In order to study the efect of acidity and alkalinity on the test, DMSO containing 4-PyOH and PBS bufer solution with diferent pH values were mixed (V DMSO /V PBS � 7 : 3) to obtain a 4-PyOH stock solution (10 μM).Based on the fuorescence spectra measurements recorded for the probe in diferent pH solutions (Figure S3), it was observed that as the pH gradually decreased, the fuorescence intensity of the probe at 525 nm diminished.In comparison, the fuorescence intensity near 385 nm increased and the fuorescence color transitioned from yellow to blue.Conversely, when the pH value reached 13.0, the fuorescence peak at 385 nm completely disappeared, and the solution's color deepened.A blue shift in the fuorescence spectrum was observed with decreasing pH, while an opposite red shift occurred with increasing pH.Tese spectral shifts were likely attributed to proton movement on the hydroxyl groups within the probe.However, within the pH range of 2.0-12.0, the probe exhibited relative stability and adaptability to complex acidbase environments.Tese fndings suggested that the probe may fnd applications in diverse detection scenarios.To further investigate the FL stability of the probe, as well as with the F − in THF, the FL intensity at 450 nm was continuously (0-10 min) measured every 30 s. Te corresponding FL spectra and the variation tendency are summarized in Figure S4.Te results showed that the intensity increased signifcantly in the initial 30 s after the addition of F − and stabilized after about 2 min, implying a fast response speed of probe 4-PyOH to F − .Te photostability is also crucial and is an important factor to measure the fuorescence properties of the compound.Te fuorescence intensity of probe 4-PyOH was tested with a three-purpose ultraviolet analyzer for diferent durations of irradiation.Te test results are shown in Figure S5.With the illumination time ranging from 0 to 180 min, the fuorescence intensity of the compound basically did not change, indicating that the probe 4-PyOH had good photostability.
To enlarge the applicable situation, the infuence of temperature on the probe detection of F − was investigated by proceeding with the detection in three temperature solutions (0 °C, 20 °C, and 40 °C) and the results showed that Journal of Analytical Methods in Chemistry temperature would not infuence the detection efect (Figure S6).According to the thermogravimetric analysis (TGA) test, compound 4-PyOH displayed a thermal decomposition (T d ) temperature at 300 °C (Figure S7), which implied a good probe thermal stability and longtime storage possibility.

Detection Mechanism.
Te recognition mechanism was postulated as follows: upon F⁻ detection, the probe initially establishes hydrogen bonds with fuoride ions.Subsequently, a deprotonation reaction induced by fuoride ions occurs, leading to the removal of protons from the phenolic hydroxyl group and the formation of phenolic oxygen anions.Similarly, due to the comparatively lower electron density at the 4-position of pyrene, the protons attached to the phenolic hydroxyl group at the 4-position are more prone to dissociation, rendering them more acidic.To validate the proposed reaction mechanism, 1 H-NMR titration experiments and FTIR were conducted.Te F − induced deprotonation mechanism between fuorine and the 4-PyOH was further researched by titration of the 1 H-NMR spectra of 4-PyOH in d 6 -DMSO with diferent amounts of F − (1.0 eq, 2.0 eq, and 3.0 eq).As shown in Figure 2, the 1 H-NMR signal of the phenolic proton of 4-PyOH (10.6 ppm) vanished following the addition of F − (1.0 eq), but the typical peaks for other hydrogen remained unchanged.Further increase of F − , the mostly pyrenyl signals shifted upfeld (dominated by a through-bond efect) [35] except that the one near the hydrogen bond (dominated by a through-space impact) [36] and a new signal located at 16.5 ppm corresponding to HF 2 − could be observed.In the frst step, a hydrogen-bonded species is formed between the F-and OH proton in the presence of lower equivalents of fuoride ions, followed by deprotonation at higher equivalents of fuoride ions.Hence, the results of the titration experiment indicated that 4-PyOH adopted a hydrogen bond to interact with F − at the phenolic OH group, and then F − induced deprotonation to generate its phenolate anion.
Te sharp peak at 3001 cm −1 corresponds to OH stretching frequency in 4-PyOH (Figure S8).Similarly, the OH stretching frequencies are broadened and enlarged due to the binding of fuoride ions to the hydroxyl hydrogen, which is reported that the hydrogen bonding interactions enhance the IR intensity for bands related to vibrational modes of functional groups directly involved in the hydrogen bonding [37].

Applications.
To facilitate practical application, a disposable and portable 4-PyOH-based test paper was developed.Te test paper exhibited distinct color changes and alterations in the UV-vis spectra of 4-PyOH upon exposure to increasing concentrations of F − ions in organic solvents.Tis enabled the visual and quantitative detection of F − ions using the test paper.Te selective interaction between F − ions and the hydroxyl group of 4-PyOH caused the observed changes.Te test paper demonstrated high sensitivity, a low detection limit, and minimal interference from other ions commonly found in organic solvents.Te simplicity and convenience of the test paper ofer a promising approach for on-site F − ion detection in various applications such as environmental monitoring and industrial safety.
Te 4-PyOH-based test paper for monitoring F − ions in THF via distinct color variation under daylight conditions is illustrated in Figure 3. Te test paper was immersed in THF solutions with varying concentrations of F − ions (ranging from 0 mmol/L to 200 mmol/L).Upon immersion, the test paper exhibited a gradual transition in color from colorless to yellow.Te observed color change was directly correlated with the concentration of F − ions in THF.Higher F − ion concentrations resulted in more pronounced color changes.Tis distinctive and discernible color variation can be utilized as a visual pattern for quantitatively analyzing unknown F − concentrations in THF.Te 4-PyOH-based test paper demonstrated its potential as a practical and efcient tool for on-site monitoring of F − ions in THF.In order to better digital representation of the test paper color intensity Journal of Analytical Methods in Chemistry change, each paper trip is photographed using Photoshop software to see its color value (R.G.B and Lab) and the data are summarized in Table S2.Tis approach ofers a promising strategy for rapid and qualitative F − ion detection in THF, with potential applications in various felds such as chemical synthesis, pharmaceutical manufacturing, and industrial processes.
Te self-made cut test paper was dipped into a mixed solution containing diferent ions (Cl − , Br − , I − , HSO Tese experimental results demonstrated that the test paper can instantly and selectively detect F − ions in THF (tetrahydrofuran) and holds potential for practical applications.

Conclusion
In summary, the fuorescent probe 4-PyOH was synthesized by functionalizing the 4 positions of the pyrene core, enabling it to recognize trace amounts of F − ions selectively.Te probe 4-PyOH demonstrated excellent selectivity and sensitivity for F − ions, with a detection limit as low as 3.06 × 10 −7 M. Te presence of F − ions can be easily identifed with the naked eye using 4-PyOH.Furthermore, the probe 4-PyOH exhibited good stability and remained unafected in solutions with a pH range of 2.0-12.0.Additionally, the probe 4-PyOH was successfully incorporated into the test paper for detecting Fions in organic solvents, yielding highly satisfactory results.Te development of more novel fuorescent probes based on 4-PyOH is anticipated, which could serve as a reference for future integration of multifunctional detection within a single probe molecule.In future work, based on the fuorescence characteristics of pyrene, more water-soluble probes were designed for the detection of various samples, including biological imaging.We believe that the molecular-level understanding of the sensing action and photophysical properties will facilitate the rational design of chemosensors.

3. 1 .
Fluorine Ion Sensing Properties of Probe 4-PyOH.Te fuorescence spectra of 4-PyOH were measured with the increase of F − concentration by titration experiments.As shown in Figure 1, with the gradual increase of F -content, 2

3 −
, AC − , S 2− , ion concentration is 100 mmol/L) to observe the selectivity and sensitivity of the test paper towards F − .As shown in Figure4, F − caused evident color changes on the test paper, with a reaction time as short as approximately three seconds.No color changes were observed in other control experiments with diferent ions on the test paper.